Molecular recognition, the mechanisms by which biological macromolecules interact either with each other or with other various small substrates with high specificity and affinity to form specific molecular complexes, constitutes the foundation for all processes in living organisms. Knowledge of the mechanisms responsible for protein-ligand recognition phenomena and an accurate quantification of the energetics, which drive the complexation will help to facilitate the discovery, design and development of modern pharmaceuticals. The aim of this project is to use novel THz cluster spectroscopy facilities for a fundamental systematic exploration of the driving forces associated with molecular recognition mechanisms and the competing micro-solvation processes for organic molecules with functional groups representative for biological systems.
The non-covalent forces stabilizing weakly bound clusters are up to 100 times weaker than typical covalent bonds and the class of large-amplitude intermolecular vibrational transitions introduced by complexation is observed in the challenging THz spectral region. The interaction strength, directionality and anharmonicity of hydrogen bonds and/or van der Waals interactions can be probed directly via these large-amplitude vibrational modes arising from hindered rotational and trans-lational motion of the subunits in the weakly bound cluster molecules. THz spectral signatures help to characterize the intermolecular potential energy surface spanned by the subunits with high accuracy and yield rigorous benchmarks for high-level quantum chemical calculations.
A B. Sc. or M. Sc. project would typically involve a combination of quantum chemistry and experiments including the following aspects:
- operation of state-of-the-art low-temperature THz/IR
cluster spectroscopy setups
- high vacuum technology, cryogenic materials, optics
- handling of cryostats and THz detectors at 4 Kelvin
- high-level quantum chemical force field calculations
employing the DTU high-performance computers
- spectral interpretation based on concentration
dependency, isotopic labelling, diffusion
experiments and exploratory spectral predictions
Please read our "popular" article for DTU Chemistry's annual report 2019 below
